Ga-68 PSMA PET/CT in recurrent high-grade gliomas: evaluating PSMA expression in vivo.

PURPOSE: We planned this prospective study to evaluate PSMA expression in recurrent high-grade gliomas (rHGG), including anaplastic astrocytoma and glioblastoma using Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68 (HBED-CC)]- (Ga-68 PSMA) positron emission tomography (PET), with its theranostic potential in mind. METHODS: This was a prospective study enrolling patients with clinical and MRI evidence of rHGG on follow-up. Three treated cases of HGG with RN on MRI were also included as negative controls. Abnormal tracer accumulation in the brain parenchyma, more than the contralateral hemisphere was interpreted as positive study. For semiquantitative analysis, a 3D spherical region of interest (ROI) was drawn around the site of the abnormal Ga-68 PSMA uptake, and the ratio of SUVmax of tumor (T) to SUVmax of the contralateral corresponding area (TBR) was calculated. Each patients' PSMA brain PET was fused to the corresponding MRI and reviewed for concordance. RESULTS: Thirty patients were included in the study, a total of 49 lesions were detected on MRI, and fused PET/MR images showed increased Ga-68 PSMA uptake in all these lesions. Multifocal lesions were better appreciated on fused PET-MR images, and concordance between MRI and PET was 100 % for patient and lesion-wise detection. Recurrent glioma lesions showed SUVmax and SUVmean values (median and IQR) 6.0 (4.4-8.2) and 3.3 (2.8-3.7), respectively. Lesions labeled as radiation necrosis on MRI did not show tracer accumulation. CONCLUSION: Ga-68 PSMA has potential utility for evaluating recurrence in HGG and its potential for theranostics would encourage its use in the evaluation of these patients.

Biodistribution, pharmacokinetics, dosimetry of [68Ga]Ga-DOTA.SA.FAPi, and the head-to-head comparison with [18F]F-FDG PET/CT in patients with various cancers.

PURPOSE: [68Ga]Ga-labeled fibroblast activation protein inhibitors ([68Ga]Ga-FAPi) have shown promising preclinical and clinical results in PET imaging. The present study aimed to evaluate the biodistribution, pharmacokinetics, and dosimetry of [68Ga]Ga-DOTA.SA.FAPi, another modified FAPi tracer, and performed a head-to-head comparison with [18F]F-FDG PET/CT scans in patients with various cancers. METHODS: In this prospective study, patients underwent both [18F]F-FDG and [68Ga]Ga-DOTA.SA.FAPi PET/CT scans 60 min post-injection (p.i.). Dosimetry studies were conducted in three patients using [68Ga]Ga-DOTA.SA.FAPi serial time-point imaging. The absorbed dose was calculated using OLINDA/EXM 2.2 software. Quantification of the uptake of the tracers was assessed using standardized uptake values corrected for lean body mass (SUL). RESULTS: Fifty-four patients (mean age; 48.4 years) with 14 types of cancers involving 37% breast, 24% lung, 7.4% head and neck (H&N), and remaining 31.6% patients with other histologies were evaluated prospectively. Physiological uptake of [68Ga]Ga-DOTA.SA.FAPi was observed in the liver, kidneys, pancreas, heart contents, and to a lesser extent in the lacrimals, oral mucosa, salivary glands, and thyroid glands. Uptake in the target lesions on [68Ga]Ga-DOTA.SA.FAPi scan was initiated at 10 min, and no additional lesions were detected in the delayed acquisition time points. The pancreas was the organ with the highest absorbed dose (5.46E-02 mSv/MBq). While the patient-based comparison between the radiotracers revealed complete concordance in the detection of primary, pleural thickening, bone and liver metastases, and second primary malignancy, discordant findings were observed in the detection of lymph node (7.5%), lung nodules (5.6%), and brain metastases (2%). According to the site of primary disease, patients with H&N cancers demonstrated the highest SULpeak and average (avg) values on [68Ga]Ga-DOTA.SA-FAPi which was similar to the values of [18F]F-FDG [(SULpeak: 15.4 vs. 14.2; P-0.680) (SULavg: 8.3 vs. 7.9; P-0.783)]. The lowest uptake was observed in lung cancers with both the radiotracers [(SULpeak: 5.8 vs. 7.4; P-0.238) (SULavg: 4.9 vs. 5.3; P-0.313)]. A significantly higher SULpeak and SULavg for brain metastases to normal brain parenchyma ratios were observed on [68Ga]Ga-DOTA.SA.FAPi in contrast to the [18F]F-FDG values {SULpeak: median: 59.3 (IQR: 33.5-130.8) versus 1.5 (1-2.3); P-0.028}. Except for brain metastases, comparable SULpeak and average values were noted between the radiotracers in all other regions of metastases with no significant difference. CONCLUSION: [68Ga]Ga-DOTA.SA.FAPi is a promising alternative among the FAPI class of molecules and performed well as compared to standard-of-care radiotracer [18F]F-FDG in the diagnosis of various cancers.

Role of 18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Predicting Residual Disease Posttreatment Completion in Retinoblastoma Patients.

Background: Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. Magnetic resonance imaging (MRI) of the orbit and brain is the preferred imaging modality to diagnose and define extent of disease as well as to assess response to therapy. Sometimes, it may be difficult to differentiate the presence of active residual disease from therapy-related changes based on posttreatment completion MRI. Materials and Methods: RB patients who completed treatment between January 2017 and October 2019 were retrospectively analyzed. We evaluated the utility of F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) to predict active disease in RB patients who continued to have residual disease on MRI at completion of treatment. Results: Out of the 89 patients who completed treatment, dilemma regarding remission status was present in 11 children. All 11 patients underwent FDG-PET-CT. None of them had evidence of metabolically active disease in the orbit, optic nerve, brain, or rest of the body. After a median follow-up of 24 months, no children developed any evidence of disease progression in the form of local or distant relapse. Conclusion: Our results showed that in MRI doubtful cases, a nonavid FDG-PET is reassuring in avoiding further therapy as long as close follow-up can be ensured. FDG-PET-CT may emerge as a useful functional modality to predict disease activity in RB.

First-in-Human Experience With 177Lu-DOTAGA.(SA.FAPi)2 Therapy in an Uncommon Case of Aggressive Medullary Thyroid Carcinoma Clinically Mimicking as Anaplastic Thyroid Cancer.

ABSTRACT: A 56-year-old man was diagnosed with calcitonin negative, plasma chromogranin A-positive, immunohistochemistry-negative, high-grade MTC (medullary thyroid cancer) behaving clinically like anaplastic thyroid cancer and presented with progressive disease after conventional therapies. A theranostic approach of 68Ga-DOTA.SA.FAPi-guided 177Lu-DOTAGA.(SA.FAPi)2 radionuclide therapy was administered on compassionate grounds as per the Declaration of Helsinki because known standard lines of treatment were ineffective. Treatment with a single cycle of 1.65 GBq 177Lu-DOTAGA.(SA.FAPi)2 demonstrated a sustainable reduction in the neck mass with significant improvement in the quality of life of the patient. 177Lu-DOTAGA.(SA.FAPi)2 is a potential theranostic option for high-grade MTC refractory to standard therapeutic options.

Pulmonary sclerosing pneumocytoma mimicking carcinoid on preoperative imaging in a 14-year-old female.

Pulmonary sclerosing pneumocytoma is a rare benign neoplasm of the lung, commonly occurs in middle-aged persons with a marked female predominance. Earlier, it was known as sclerosing hemangioma. Here, we present a case of pulmonary sclerosing pneumocytoma which was diagnosed as carcinoid of the lung, based on imaging, in a 14-year-old female. Besides radiology, the uniqueness of this case lies in the young age (14 years) of the patient. She was presented with a 3.3 × 2.5 × 2.2 cm soft tissue density mass with a tiny speck of calcification in the anterior basal segment of the lower lobe of the right lung. Based on imaging findings on fluorodeoxyglucose positron emission tomography (FDG PET) scan and DOTANOC scan, a diagnosis of carcinoid was made. We performed a video-assisted thoracoscopic right lower lobectomy. Histopathological examination showed features of pulmonary sclerosing pneumocytoma. Surgery is an established method of treatment for pulmonary sclerosing pneumocytoma. Enucleation, lobectomy, sleeve resection are possible treatment options. To define the role of adjuvant therapy, further direct evidence is required. The metastatic potential of this disease is yet to be established.

68Ga-PSMA PET/CT Scan on Postoperative Assessment of Sinonasal Glomangiopericytoma.

ABSTRACT: Prostate-specific membrane antigen (PSMA) is expressed on the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms. Positive intense uptake on PET/CT imaging with 68Ga-labeled PSMA is noted in a patient with sinonasal glomangiopericytoma, and the same is noted to be absent following complete surgical excision. 68Ga-PSMA PET/CT may be a useful tool for early recurrence identification, differentiating recurrence from surgical site reparative tissues, and peptide receptor radionuclide therapy of residual lesions.

Pterygoid Base Pneumatization Simulating Residual Disease-A Pitfall of Structural Imaging in Juvenile Nasal Angiofibroma.

ABSTRACT: As prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasopharyngeal angiofibroma, it is commonly used for specifically differentiating recurrences from surgical site reparative tissues. Postoperative contrast-enhanced MRI revealed a residual disease in the left pterygoid base, but there was no PET/CT uptake with 68Ga-labeled PSMA at the same site. In retrospect, in comparison with preoperative PET/CT, it was found that the pterygoid base pneumatization was showing enhancement in contrast-enhanced MRI and not in functional PSMA. Postoperative 68Ga-PSMA PET/CT is a useful clinical tool in ambivalent diagnostic conditions avoiding morbidities.

Designing and Comparing Performances of Image Processing Pipeline for Enhancement of I-131-metaiodobenzylguanidine Images.

OBJECTIVE: An image processing pipeline can have more than one image processing technique in sequence, and the output of the first technique becomes input for the next technique and so on. In this study, we have designed and compared the performances of image processing pipelines for enhancement of I-131-metaiodobenzylguanidine (mIBG) images. MATERIALS AND METHODS: Five different image processing pipelines (A [Gaussian filter, normalization], B [histogram specification (image 1), Gaussian filter, normalization], C [histogram specification (image 2), Gaussian filter, normalization], D [{histogram specification (image 3), Gaussian filter, and normalization], and E [histogram specification (image 4), Gaussian filter, normalization]) were designed and their performances were evaluated on I-131-mIBG images (n = 122). The image quality was assessed objectively using Perception-based Image Quality Evaluator (PIQE) score and subjectively (on scale 1-4) by two nuclear medicine physician. Sign test was applied to find the statistically significant difference between the image quality obtained using image processing pipelines. We applied test of proportion to compute difference in proportion of image quality score assigned to images obtained using image processing pipelines. RESULTS: Based on PIQE score, the quality of images obtained using all the five image processing pipelines were significantly better than that of input images (P < 0.001). The highest image quality score (=4) was assigned maximum number of times (n = 90) to the images obtained using image processing pipeline D and was significantly different from that of the second best image processing pipeline E (P = 0.015). CONCLUSIONS: The image processing pipeline D was found to be better for enhancement of I-131-mIBG images.

Fusion 68Ga-DOTANOC PET/MRI in Primary Juvenile Nasal Angiofibroma.

ABSTRACT: Somatostatin cell surface receptors are expressed in many different benign and malignant tumors and are often exploited for imaging and therapy of neuroendocrine tumors. A 17-year-old adolescent boy with clinicoradiologically diagnosed JNA (juvenile nasopharyngeal angiofibroma) also underwent 68Ga-DOTANOC PET to explore somatostatin cell surface receptors' expression and its theranostic potential. Fusion PET/MRI, a novel imaging technology, exactly depicted the anatomical extensions of the tumor with avid DOTANOC uptake. This software-based fusion technique is advantageous for easy early recurrence identification, better delineation from postoperative scar tissue, for planning the exact target volumes for stereotactic radiotherapy therapy of inoperable/residual/recurrent JNAs in the future.

Metastatic Medulloblastoma: 18F-FDG and 68Ga-DOTANOC PET/CT in Response Evaluation.

ABSTRACT: We describe the utility of molecular imaging with 18F-FDG and 68Ga-DOTANOC PET for treatment response assessment in a case of metastatic medulloblastoma. 18F-FDG and 68Ga-DOTANOC PET/CT revealed extensive metastases to bone and bone marrow. Patient subsequently had an excellent response to systemic chemotherapy which was evidenced by resolution of tracer-avid skeletal lesions on both FDG and DOTANOC PET/CT.

F-18 ML-104 tau PET imaging in mild cognitive impairment.

OBJECTIVE: This study was undertaken to evaluate the tau distribution patterns in patients with amnestic mild cognitive impairment (aMCI) using PET radiotracer F-18 ML-104. MATERIALS AND METHODS: Thirty patients, clinically diagnosed as aMCI [mini mental state evaluation ≥24] in the neurology or geriatric memory clinics, were included in the study. Each aMCI patient underwent F-18 fluorodeoxyglucose and F-18 ML-104 tau PET. Standardized uptake value ratios for cortical gray matter regions were evaluated for F-18 ML-104 tau PET and compared with normal controls and with early Alzheimer's disease (AD) patients (used from a previous study). RESULTS: aMCI revealed significantly higher standardized uptake value ratios in both medial temporal cortices, precuneus and posterior cingulate cortices in comparison to normal controls and a significantly lesser binding in bilateral medial and lateral temporal, precuneus and posterior cingulate cortices in comparison to early AD. A negative correlation was noted between F-18 fluorodeoxyglucose uptake and F-18 ML-104 retention in the precuneus and posterior cingulate cortices in aMCI, while F-18 ML-104 retention and mini mental state evaluation scores revealed a moderate negative correlation in the posterior cingulate cortices. CONCLUSION: We could demonstrate a significant increase in cortical tau deposition in aMCI patients in comparison to normal controls, thus providing in vivo evidence of the underlying pathological process in this subgroup of patients with high probability of conversion to AD.

Physiological PSMA Uptake in the Tubarial Salivary Glands and Its Implications in the PARIS Protocol-A First Study of Its Kind!

OBJECTIVES: Because prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasal angiofibroma (JNA), PSMA PET/CT is commonly used in the postoperative setting using the postoperative angiofibroma radionuclide imaging study protocol. Our study aims to illustrate physiological PSMA ligand uptake distribution characteristics in the salivary glands, specifically the tubarial glands with tumor, to aid in accurate PSMA PET/CT analysis. STUDY DESIGN: Forty-three consecutive patients who underwent a dedicated head and neck spot PSMA PET/CT for JNA were evaluated retrospectively. PSMA SUVmax values in the tumor, tubarial, parotid, submandibular, and sublingual salivary glands were determined visually and quantitatively. RESULTS: All the tumors and the salivary glands showed increased tracer uptake. The median SUVmax ± SD ratios of the tumor, right and left tubarial gland, right and left parotid gland, right and left submandibular gland, and right and left sublingual gland were 2.7 ± 0.8 (range, 0.5-7.5), 3.8 ± 1.9 (range, 0.9-8.1), 4.7 ± 2.1 (range, 0.8-7.4), 9.5 ± 4.8 (range, 3.2-21.9), 9.2 ± 4.7 (range, 2.9-18.9), 10.4 ± 5.7 (range, 3.5-25.4), 10.4 ± 5.5 (range, 3.7-26.4), 6 ± 4.1 (range, 1.3-20.6), and 6.5 ± 4.2 (range, 1.8-19.7), respectively. The uptake in the tubarial glands was comparable with that of the tumor but less compared with other major salivary glands. CONCLUSIONS: Ours is the first study demonstrating the quantitative uptake of tubarial salivary glands in detail. Because the tubarial glands uptake and the anatomical location are similar to that of the tumor, these physiological uptakes must be borne in mind to circumvent false-positive interpretations and care must be given during the planning of stereotactic radiotherapy for JNAs.

Thoracic Extradural Paraganglioma Localized on 68Ga-DOTANOC PET/CT.

ABSTRACT: We present the case of a 33-year-old woman with complaints of headache and palpitations with raised urinary catecholamines. Ultrasound of the abdomen was noncontributory, and the patient was referred for 68Ga-DOTANOC PET/CT, which revealed tracer accumulation in the thecal sac/spinal canal at D5-D7 level, suggestive of a thoracic paraganglioma. MRI of the spine subsequently confirmed the presence of an extradural mass in the spinal canal extending from D4 to D8.

68 Ga DOTANOC PET/CT Scan in Primary Juvenile Nasopharyngeal Angiofibroma - A Pilot Study.

OBJECTIVES/HYPOTHESIS: Somatostatin receptors (SSTRs) are highly expressed in neuroendocrine tumors and is exploited for its imaging and treatment. SSTRs expression is also demonstrated in diverse benign and malignant tumor cell types and proliferating peri-tumoral vessels. Similarly, Juvenile Nasopharyngeal Angiofibroma (JNA) expresses different SSTRs and may be utilized for its imaging and treatment using DOTA, 1-Nal3-octreotide (DOTANOC)-PET/CT scan. STUDY DESIGN: Prospective cohort. METHODS: Nineteen clinico-radiologically diagnosed primary JNA patients underwent a 68 Ga-DOTANOC PET-CT scan. Using a dedicated PET/CT scanner, a low-dose head and neck spot CT scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi(74-111 MBq) of DOTANOC. The primary objective was to assess the intensity and pattern of DOTANOC uptake in these patients. RESULTS: DOTANOC expression was noted in all cases (n = 19) of primary JNA (100%). The mean (SD) DOTANOC SUVmax ratio of tumor and background was 6.9+/-1.4(range, 3.8-9.5). Intra-cranial extension in all 13/19 patients was prominently visualized due to the absence of DOTANOC uptake in the brain. Compared to the background all stages of JNA showed significant DOTANOC uptake (P < .0001). No difference in uptake between advanced-stage tumors and early tumors was noted (P = .47). A statistically non-significant negative trend was noted for decreasing uptake with increasing age (Spearman correlation coefficient, r = -0.19). CONCLUSIONS: This first study of 68 Ga-DOTANOC-PET/CT scan in JNA demonstrates consistent and reliable uptake activity in all patients irrespective of age and stage. This opens up possibilities to physiological diagnostic imaging with a promise of greater specificity and sensitivity and may have applications in ambivalent diagnostic situations such as the detection of recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1509-1515, 2021.

68Ga-Prostate-Specific Membrane Antigen PET/CT in Sinonasal Glomangiopericytoma-Exploring Theranostic Avenues!

ABSTRACT: Prostate-specific membrane antigen (PSMA) is expressed in the tumor-associated endothelial neovasculature of various nonprostatic benign and malignant neoplasms. A 25-year-old man with recurrent sinonasal glomangiopericytoma underwent whole-body 68Ga PSMA PET/CT to explore its theranostic role. There was intense PSMA uptake (SUVmax = 23.9) noted in the tumor. The uptake was more than that of the salivary glands, lacrimal glands, aorta, spleen, and the liver. Performance of PSMA PET/CT in sinonasal glomangiopericytoma opens up new frontiers concerning radiological imaging, early recurrence identification, and perhaps even radioligand therapy of residual/recurrent tumors.

Fusion 68Ga-Prostate-Specific Membrane Antigen PET/MRI on Postoperative Surveillance of Juvenile Nasal Angiofibroma.

Prostate-specific membrane antigen (PSMA) is expressed universally in juvenile nasopharyngeal angiofibroma (JNA). As contrast enhancement of postoperative scar is common with contrast-enhanced MRI (CEMRI), diagnosis of residual/recurrent JNA remains perplexing. Prostate-specific membrane antigen PET targets only the neovasculature and may aid in resolving this dilemma. Positive contrast enhancement on CEMRI was noted in a patient after 30 years of initial surgery, simulating recurrence. However, there was no abnormal uptake in PSMA scan, which was confirmed by biopsy as postoperative fibrosis. Ga-PSMA PET/MRI fusion may be an easy and novel technique to aid in differentiating residual/recurrent disease from surgical site reparative tissue.

An Unusual Case of Synovial Sarcoma with Breast Metastasis: Findings on Positron Emission Tomography-Computed Tomography.

Synovial sarcomas are aggressive soft-tissue tumors with the propensity for metastases at presentation or later course of disease. The most common site of metastases is lung, followed by lymph node and bone. It rarely metastasizes to the liver and to the brain. Breast metastases from extramammary tissue are extremely rare, more so from synovial sarcoma. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) plays a very important role in diagnosing occult metastasis in sarcomas. Histopathological diagnosis and translocation studies are important to confirm the diagnosis. We present a case of synovial sarcoma who underwent 18FDG PET/CT which showed occult metastasis to the breast.

Clinical Utility of 68Ga-DOTANOC Positron Emission Tomography-Computed Tomography Scan on Postoperative Assessment of Juvenile Nasal Angiofibroma.

Somatostatin cell surface receptors are expressed on the peritumoral vessels of various benign and malignant neoplasms including angiofibromas. Positive initial uptake on positron emission tomography-computed tomography (PET/CT) imaging with 68Ga-labeled DOTANOC is noted in a patient with juvenile nasal angiofibroma (JNA), and the same is noted to be absent following complete surgical excision. Functional 68Ga-DOTANOC PET/CT may be an early useful tool for JNA residual/recurrence identification and precise postoperative surveillance.

Comparison of Prostate-Specific Membrane Antigen PET/CT and Contrast-Enhanced Magnetic Resonance Imaging in Follow-up Assessment of Juvenile Nasal Angiofibroma-A Novel Pilot Study.

PURPOSE/BACKGROUND: The specific identification of residual/recurrent juvenile nasal angiofibroma (JNA) following surgical treatment remains difficult. Contrast MRI and CT may not enable the differentiation of tumor from postsurgical reparative tissue. Functional imaging with prostate-specific membrane antigen (PSMA) PET/CT targeting tumor-associated neovasculature has recently demonstrated universal positive uptake in primary JNA and offers promise of greater accuracy in the detection or exclusion of recurrent/residual JNA. METHODS: In this prospective study, 18 postsurgical JNA patients with high suspicion for residual disease evinced by follow-up MR scan, or nasal endoscopy, or recent epistaxis during September 2018-November 2019 were included. All patients underwent head and neck spot PSMA PET/CT imaging. Postcontrast enhancement of a definite lesion was considered as a criterion for residual/recurrent tumor in contrast-enhanced MRI (CEMRI). In PSMA PET/CT, any abnormal uptake apart from physiological sites in the head and neck was considered as residual lesions. Radiological results were categorized as negative, suspicious, and residual/recurrent tumors. Any discrepancy between CEMRI and PSMA was resolved by surgical biopsies. The sensitivity, specificity, and positive and negative predictive values were separately calculated for CEMRI and PSMA PET/CT for diagnosing residual lesions. The interrater agreement κ value was also calculated. RESULTS: On CEMRI evaluation, 14 of 18 patients had residual tumors, 2 had suspicious residual lesions, and 2 had normal postoperative scans. On PSMA PET/CT, 12 of 18 patients had residual tumors, and 6 had normal negative scans. Surgical biopsy in all 4 discordant cases was negative for tumors and revealed only fibrosis. In 1 patient with residual tumor on both scans, discrepancy was noted with regard to tumor extent demonstrated by the 2 scans, and further surgical excision confirmed the imaging findings of PSMA PET/CT as accurate. The sensitivity, specificity, and positive and negative predictive values of CEMRI were 100%, 33.33%, and 75% and 100%, respectively. The sensitivity, specificity, and positive and negative predictive values of PSMA PET/CT were 100% for all parameters. The interrater agreement between the 2 tests (κ) is 0.5 (95% confidence interval, 0.19-0.81). CONCLUSIONS: The Ga-PSMA PET/CT is noted as more specific than the current standard of CEMRI in the identification of residual/recurrent JNA. It is the first radionuclide imaging scan that has found application in postoperative assessment of JNA. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI/2018/08/015479).